After Heparin: - The Pew Charitable Trusts

—Chapter 1—
Case study 4
Biochimica Opos: Antibiotic ingredients sourced
from undisclosed suppliers
In the mid- to late 1990s, an Italian pharmaceutical manufacturer making bulk antibiotics for the U.S.
market deliberately falsified records to conceal from the FDA its use of undisclosed manufacturing
sites. 213,214 The manufacturer, Biochimica Opos (Opos), was at the time a wholly owned subsidiary of
French drug company Roussel-Uclaf. 215
The FDA visited Opos’ factory in Agrate Brianza, Italy, in May 1996 for a post-approval inspection
and became concerned by apparent inconsistencies in information given to them by employees
at the plant, including records documenting where the materials used to make one antibiotic—
cefaclor—had been manufactured. 216 In October 1996, Roussel-Uclaf admitted it had not produced
cefaclor in accordance with its approved marketing application, and also admitted to similar infractions
for antibiotics clindamycin and minocycline for the U.S. market. The company recalled the
three products and withdrew its approved marketing applications. 217
The case was referred to the FDA’s Office of Criminal Investigations in 1997 218 and culminated in
multiple felony charges, including conspiracy and distribution of adulterated drugs in interstate
commerce with intent to defraud or mislead. 219 On October 19, 2001, five years after the FDA’s
initial inspection, Roussel-Uclaf’s successor, Aventis Pharma A.G., pleaded guilty to these charges
and was ordered to pay a $23,193,600 criminal fine and forfeit $10 million in proceeds to the
U.S. government. 220
Roussel-Uclaf had falsified batch production records, raw material logs and work orders to create
the appearance that all of its manufacturing occurred at sites designated in its approved U.S.
marketing application. 221 In reality, the company was outsourcing the manufacture of materials used
to make cefaclor to facilities in Italy, France and Romania that were not listed in its application or
inspected by the FDA. 222 This put Opos in knowing breach of its approved manufacturing pathway.
Further, Opos was found to have used a different, unapproved chemical in place of a required
chemical for cefaclor processing. 223
The Opos case represented the first time a foreign corporation making a drug product entirely outside
of the United States received a criminal punishment for defrauding the FDA. 224 One FDA agent
reported that the investigation was made difficult by its foreign nature; in particular, some potential
witnesses were not subject to U.S. subpoena. 225 However, U.S. investigators did receive assistance
from foreign authorities in accessing important documents and witnesses. 226 To support this type of
cooperation, the FDA should be allowed to share all information, including trade secret information,
in a protected manner with foreign agencies—a general authority that it does not currently have
(see section 2.4.3). 227 As drug manufacturing becomes increasingly globalized, international collaboration
is essential for improving oversight and identifying wrongdoing.
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Pew Health Group